Abstract

2056

Clinical efficacy of chemotherapy for androgen-independent prostate cancer (AIPC) is often limited by cellular drug resistance conferred through loss of dependency on the androgen receptor for growth. Consequently, improved chemotherapeutic management of AIPC expressing cancer cells would require agents that target prostate cancer cells regardless of their dependence on the androgen receptor for growth. We have identified a new class of potential chemotherapeutic agents that are acetamide derivatives that exhibit varying degrees of potency and selectivity in vitro against LNCaP prostate cancer cells, while noncancerous CV-1 monkey kidney epithelial cells show reduced sensitivity. Trypan blue dye exclusion was used to determine cytotoxicity, and in addition, TUNEL assay was performed to confirm apoptosis. Results show IC50 values of < 0.05 μM, 0.38 μM, and 0.77 μM in LNCaP and > 10.0 μM, 1.30 μM, and 0.48 μM in CV-1 cells for compound A-1, A-2, and A-3, respectively. Following 10 μM continuous drug exposure for 24 h, there is notable DNA fragmentation in cells treated with A-2 and A-3 as seen with the TUNEL assay. When drug was washed out after a 24 h exposure and replaced with fresh media containing no drug, the prostate cancer cells were unable to recover from the cytotoxic effects of the acetamide drugs. These data merit further investigation into the potential therapeutic efficacy of this class of compounds with in vivo studies.